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In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line.

Nanjo S, Nakagawa T, Takeuchi S, Kita K, Fukuda K, Nakada M, Uehara H, Nishihara H, Hara E, Uramoto H, Tanaka F, Yano S - Cancer Sci. (2015)

Bottom Line: By using A925LPE3 cells with luciferase gene transfection, we established in vivo imaging models for pleural carcinomatosis, bone metastasis, and brain metastasis, all of which are significant clinical concerns of advanced EML4-ALK lung cancer.Interestingly, crizotinib caused tumors to shrink in the pleural carcinomatosis model, but not in bone and brain metastasis models, whereas alectinib showed remarkable efficacy in all three models, indicative of the clinical efficacy of these ALK inhibitors.Our in vivo imaging models of multiple organ sites may provide useful resources to analyze further the pathogenesis of EML4-ALK lung cancer and its response and resistance to ALK inhibitors in various organ microenvironments.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.

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Brain metastasis model of A925LPE3/Eluc cells and efficacy of anaplastic lymphoma kinase–tyrosine kinase inhibitors. A925LPE3/Eluc cells were inoculated into the cerebrum of SCID mice. (a) Macroscopic appearance of brain tumors. (b) Microscopic appearance of brain lesions (×200). (c) Mice were treated orally with control (n = 5), 50 mg/kg crizotinib (n = 5), or 25 mg/kg alectinib (n = 5). Treatment was given daily on days 11–40. Luminescence was evaluated twice per week. Bars indicate standard error. (d) Appearance of representative mice is shown.
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fig06: Brain metastasis model of A925LPE3/Eluc cells and efficacy of anaplastic lymphoma kinase–tyrosine kinase inhibitors. A925LPE3/Eluc cells were inoculated into the cerebrum of SCID mice. (a) Macroscopic appearance of brain tumors. (b) Microscopic appearance of brain lesions (×200). (c) Mice were treated orally with control (n = 5), 50 mg/kg crizotinib (n = 5), or 25 mg/kg alectinib (n = 5). Treatment was given daily on days 11–40. Luminescence was evaluated twice per week. Bars indicate standard error. (d) Appearance of representative mice is shown.

Mentions: To create a brain metastasis model, A925LPE3/Eluc cells were inoculated into the cerebra of SCID mice, and histological examinations confirmed the presence of tumors in the cerebra (Fig.6a,b). Furthermore, luminescence was detected in the brain 11 days after tumor cell inoculation, and the luminescence increased in a time-dependent manner, reflecting tumor progression in the cranial space (Fig.6c). The mice became moribund between days 26 and 30. Daily oral treatment with 50 mg/kg crizotinib, starting on day 11, delayed the increase of luminescence, but did not decrease it, whereas daily oral treatment with 25 mg/kg alectinib, starting on day 11, significantly decreased luminescence (Fig6c,d), indicating that alectinib was highly efficacious against brain lesions produced by A925LPE3/Eluc cells.


In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line.

Nanjo S, Nakagawa T, Takeuchi S, Kita K, Fukuda K, Nakada M, Uehara H, Nishihara H, Hara E, Uramoto H, Tanaka F, Yano S - Cancer Sci. (2015)

Brain metastasis model of A925LPE3/Eluc cells and efficacy of anaplastic lymphoma kinase–tyrosine kinase inhibitors. A925LPE3/Eluc cells were inoculated into the cerebrum of SCID mice. (a) Macroscopic appearance of brain tumors. (b) Microscopic appearance of brain lesions (×200). (c) Mice were treated orally with control (n = 5), 50 mg/kg crizotinib (n = 5), or 25 mg/kg alectinib (n = 5). Treatment was given daily on days 11–40. Luminescence was evaluated twice per week. Bars indicate standard error. (d) Appearance of representative mice is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376432&req=5

fig06: Brain metastasis model of A925LPE3/Eluc cells and efficacy of anaplastic lymphoma kinase–tyrosine kinase inhibitors. A925LPE3/Eluc cells were inoculated into the cerebrum of SCID mice. (a) Macroscopic appearance of brain tumors. (b) Microscopic appearance of brain lesions (×200). (c) Mice were treated orally with control (n = 5), 50 mg/kg crizotinib (n = 5), or 25 mg/kg alectinib (n = 5). Treatment was given daily on days 11–40. Luminescence was evaluated twice per week. Bars indicate standard error. (d) Appearance of representative mice is shown.
Mentions: To create a brain metastasis model, A925LPE3/Eluc cells were inoculated into the cerebra of SCID mice, and histological examinations confirmed the presence of tumors in the cerebra (Fig.6a,b). Furthermore, luminescence was detected in the brain 11 days after tumor cell inoculation, and the luminescence increased in a time-dependent manner, reflecting tumor progression in the cranial space (Fig.6c). The mice became moribund between days 26 and 30. Daily oral treatment with 50 mg/kg crizotinib, starting on day 11, delayed the increase of luminescence, but did not decrease it, whereas daily oral treatment with 25 mg/kg alectinib, starting on day 11, significantly decreased luminescence (Fig6c,d), indicating that alectinib was highly efficacious against brain lesions produced by A925LPE3/Eluc cells.

Bottom Line: By using A925LPE3 cells with luciferase gene transfection, we established in vivo imaging models for pleural carcinomatosis, bone metastasis, and brain metastasis, all of which are significant clinical concerns of advanced EML4-ALK lung cancer.Interestingly, crizotinib caused tumors to shrink in the pleural carcinomatosis model, but not in bone and brain metastasis models, whereas alectinib showed remarkable efficacy in all three models, indicative of the clinical efficacy of these ALK inhibitors.Our in vivo imaging models of multiple organ sites may provide useful resources to analyze further the pathogenesis of EML4-ALK lung cancer and its response and resistance to ALK inhibitors in various organ microenvironments.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.

Show MeSH
Related in: MedlinePlus